Dataset Information

Pial Collateral Reactivity During Hypertension and Aging: Understanding the Function of Collaterals for Stroke Therapy.

ABSTRACT: We investigated vasoactive properties of leptomeningeal arterioles (LMAs) under normotensive conditions and during hypertension and aging that are known to have poor collateral flow and little salvageable tissue.LMAs, identified as distal anastomotic arterioles connecting middle and anterior cerebral arteries, were studied isolated and pressurized from young (18 weeks) or aged (48 weeks) normotensive Wistar Kyoto (WKY18, n=14; WKY48, n=6) rats and spontaneously hypertensive rats (SHR18, n=16; SHR48, n=6). Myogenic tone and vasoactive responses to pressure as well as endothelial function and ion channel activity were measured.LMAs from WKY18 had little myogenic tone at 40 mm Hg (8±3%) that increased in aged WKY48 (30±6%). However, LMAs from both WKY groups dilated to increased pressure and demonstrated little myogenic reactivity, a response that would be conducive to collateral flow. In contrast, LMAs from both SHR18 and SHR48 displayed considerable myogenic tone (56±8% and 43±7%; P<0.01 versus WKY) and constricted to increased pressure. LMAs from both WKY and SHR groups had similar basal endothelial nitric oxide and IK channel activity that opposed tone. However, dilation to sodium nitroprusside, diltiazem and 15 mmol/L KCl was impaired in LMAs from SHR18.This study shows for the first time that LMAs from young and aged SHR are vasoconstricted and have impaired vasodilatory responses that may contribute to greater perfusion deficit and little penumbral tissue. These results also suggest that therapeutic opening of pial collaterals is possible during middle cerebral artery occlusion to create penumbral tissue and prevent infarct expansion.

SUBMITTER: Chan SL

PROVIDER: S-EPMC4878286 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Pial Collateral Reactivity During Hypertension and Aging: Understanding the Function of Collaterals for Stroke Therapy.

Chan Siu-Lung SL Sweet Julie G JG Bishop Nicole N Cipolla Marilyn J MJ

Stroke 20160421 6

<h4>Background and purpose</h4>We investigated vasoactive properties of leptomeningeal arterioles (LMAs) under normotensive conditions and during hypertension and aging that are known to have poor collateral flow and little salvageable tissue.<h4>Methods</h4>LMAs, identified as distal anastomotic arterioles connecting middle and anterior cerebral arteries, were studied isolated and pressurized from young (18 weeks) or aged (48 weeks) normotensive Wistar Kyoto (WKY18, n=14; WKY48, n=6) rats and s ...[more]

PMID: 27103017

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Project description:The presence of a native collateral circulation in tissues lessens injury in occlusive vascular diseases. However, differences in genetic background cause wide variation in collateral number and diameter in mice, resulting in large variation in protection. Indirect estimates of collateral perfusion suggest that wide variation also exists in humans. Unfortunately, methods used to obtain these estimates are invasive and not widely available. We sought to determine whether differences in genetic background in mice result in variation in branch patterning of the retinal arterial circulation, and whether these differences predict strain-dependent differences in pial collateral extent and severity of ischemic stroke. Retinal patterning metrics, collateral extent, and infarct volume were obtained for 10 strains known to differ widely in collateral extent. Multivariate regression was conducted, and model performance was assessed using K-fold cross-validation. Twenty-one metrics varied with strain (p<0.01). Ten metrics (e.g., bifurcation angle, lacunarity, optimality) predicted collateral number and diameter across seven regression models, with the best model closely predicting (p<0.0001) number (±1.2-3.4 collaterals, K-fold R2=0.83-0.98), diameter (±1.2-1.9 ?m, R2=0.73-0.88), and infarct volume (±5.1 mm3, R2=0.85-0.87). An analogous set of the most predictive metrics, obtained for the middle cerebral artery (MCA) tree in a subset of the above strains, also predicted (p<0.0001) collateral number (±3.3 collaterals, K-fold R2=0.78) and diameter (±1.6 ?m, R2=0.86). Thus, differences in arterial branch patterning in the retina and the MCA trees are specified by genetic background and predict variation in collateral extent and stroke severity. If also true in human, and since genetic variation in cerebral collaterals extends to other tissues at least in mice, a similar "retinal predictor index" could serve as a non- or minimally invasive biomarker for collateral extent in brain and other tissues. This could aid prediction of severity of tissue injury in the event of an occlusive event or development of obstructive disease and in patient stratification for treatment options and clinical studies.

Project description:In patients with carotid artery stenosis (CAS), the risk of stroke, its severity, and response to revascularization are strongly related to the availability of collateral blood flow. Unfortunately, there is poor agreement between observers in assessing collateral flow using flow-based imaging. We used changes in blood-oxygen-level-dependent (BOLD) MRI as a surrogate of changes in regional cerebral blood flow in response to a hypercapnic stimulus [i.e., cerebrovascular reactivity (CVR)] as indicating flow reserve ipsilateral to CAS. We hypothesized that some patients with hemodynamically significant CAS develop functional collateral flow as indicated by normalization of ipsilateral CVR. We identified 55 patients in our CVR database with various degrees of CAS assessed by angiography and classed them as <50% stenosis, 50-69% stenosis, 70-90% stenosis, >90% stenosis, and full occlusion. CVR was measured as the change in BOLD signal in response to changes in end-tidal partial pressure of CO2 (Δ BOLD/Δ PETCO2) and normalized voxel-wise relative to the mean and standard deviation of the CVR in the corresponding voxels of an atlas of 46 healthy controls (CVR z scores). CVR and z scores were then averaged over gray matter (GM) and white matter (WM) on each side of the middle cerebral artery (MCA) territory. As hypothesized, CVR varied for each severity of CAS. Ipsilateral MCA territory CVR was less than normal in each class, including that with <50% stenosis (Student t-test, two-tailed; p = 0.0014 for GM and p = 0.030 for WM), with a trend of decreasing average CVR with increasing stenosis. Remarkably, the considerable individual variability in MCA CVR included some patients with normal CVR in each class - including that with complete occlusion. We conclude that, in general, CAS depresses downstream vascular reserve, but the extent of collateralization is highly variable and not predictable from the degree of stenosis, including both <50% stenosis and complete occlusion. CVR may be the more reliable marker for recruitable collateral blood flow than degree of CAS.

Dataset Information

Pial Collateral Reactivity During Hypertension and Aging: Understanding the Function of Collaterals for Stroke Therapy.

Publications

Pial Collateral Reactivity During Hypertension and Aging: Understanding the Function of Collaterals for Stroke Therapy.

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